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Neutropenia Treatment & Management

  • Author: Christopher D Braden, DO; Chief Editor: Emmanuel C Besa, MD  more...
Updated: Feb 26, 2016

Approach Considerations

Medical care for patients with neutropenia is mostly supportive and based on the etiology, severity, and duration of the neutropenia. Fever and infections occurring as complications of neutropenia require specific treatment. Surgical care is not usually indicated but may be employed in certain contexts.

Go to Pediatric Autoimmune and Chronic Benign Neutropenia for complete information on this topic.


General Care

General measures to be taken include the following:

  • Removal of any offending drugs or agents is the most important step in most cases involving drug exposure; if the identity of the causative agent is not known, stop administration of all drugs until the etiology is established
  • Use careful oral hygiene to prevent infections of the mucosa and teeth; control oral and gingival lesion pain with saline and hydrogen peroxide rinses and local anesthetic gels and gargles
  • Avoid rectal temperature measurements and rectal examinations
  • Administer stool softeners for constipation
  • Use good skin care for wounds and abrasions; skin infections should be managed by someone with experience in the treatment of infection in neutropenic patients

Antibiotic Therapy

Start specific antibiotic therapy to combat infections. This often involves the use of third-generation cephalosporins or equivalents. Fever may be treated as an infection, as follows[5, 6, 5, 7, 3, 8, 9, 10, 11] :

  • Cefepime, meropenem or imipenem-cilastatin), or piperacillin-tazobactam can be used as a single agent
  • Agents from other antimicrobial classes (eg, aminoglycosides, fluoroquinolones, vancomycin) may be added for management of complications (eg, hypotension and pneumonia) or antimicrobial resistance (suspected or proven)

With blood culture results suspicious for resistant bacteria, early addition of the following antimicrobials may be considered:

  • Methicillin-resistant Staphylococcus aureus (MRSA) - Vancomycin, linezolid, or daptomycin
  • Vancomycin-resistant enterococcus (VRE) - Linezolid or daptomycin
  • Extended-spectrum β-lactamase (ESBL)–producing gram-negative bacteria - A carbapenem
  • Carbapenemase-producing organisms, including Klebsiella pneumoniae carbapenemase (KPC) - polymyxin-colistin or tigecycline

If the neutropenic patient’s fever does not respond within 4-5 days or if the fever recurs with the administration of broad-spectrum antibiotics after an initial afebrile interval, consider adding empiric antifungal coverage with amphotericin B (preferably lipid formulation), a broad-spectrum azole (eg, voriconazole), or an echinocandin (eg, caspofungin)

Fever in patients with low-risk neutropenia can be treated on an outpatient basis with oral antibiotics. Fluoroquinolones (eg, ciprofloxacin, ofloxacin) are oral antibiotics that are used frequently, either alone or in combination with amoxicillin-clavulanate or clindamycin. In some studies, patients are defined as being at low risk if they have all the following:

  • Known cause of neutropenia
  • Hemodynamic stability
  • Expected duration of neutropenia of less than 7 days
  • Tumor is under control
  • No comorbid conditions, nausea, vomiting, or mucositis

Colony-Stimulating Factor Therapy

Myeloid growth factors—specifically, granulocyte colony-stimulating factors (G-CSFs) and granulocyte-macrophage colony-stimulating factor (GM-CSFs)—may shorten the duration of neutropenia in patients who have undergone chemotherapy.

G-CSFs are lineage-specific for the production of functionally active neutrophils and can also be used in patients with severe, chronic neutropenia. GM-CSFs stimulate the production of neutrophils, monocytes, and eosinophils. Filgrastim and pegfilgrastim are examples of G-CSFs; sargramostim is an example of a GM-CSF. These agents are typically administered no sooner than 24 hours after chemotherapy completion. Filgrastim is often the agent of choice if a G-CSF is chosen.

The availability of filgrastim has altered the management of agranulocytosis. It has been shown to shorten the period to recovery and the duration of infection when administered before infection is established. This agent is especially indicated in the management of congenital neutropenia, idiopathic severe chronic neutropenia (SCN), and cyclic neutropenia (CN) when serious infections are involved. If the condition is mild, with only neutropenia without a serious infection, filgrastim may be withheld.

Updated guidelines for use of myeloid growth factors were made available in 2015 by the National Comprehensive Cancer Network (NCCN). Recommendations address the following areas:[48]

  • Prophylactic use in chemotherapy patients at risk of neutropenia
  • Therapeutic use for acute febrile neutropenia
  • Therapeutic use for severe chronic neutropenia

Prophylactic therapy recommendations in the 2015 NCCN guidelines are based on evaluation of the individual’s risk of febrile neutropenia associated with chemotherapy. Risk assessment should take place before the initial cycle of chemotherapy and before each subsequent cycle. Disease type, chemotherapy dose regimen, and patient risk factors should be assessed, and the intention of chemotherapy (curative, life-extending, or symptom management) noted.[48]

Prophylactic use of G-CSF is recommended for patients at high risk (>20%) of febrile neutropenia. For patients whose treatment is intended to be curative or life-extending, the recommendation is supported by class 1 evidence. CSF therapy may be considered in patients at intermediate risk (10-20), but the NCCN acknowledges that this is a difficult decision that requires careful discussion with the patient. CSF therapy appears to increase the risk of developing acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), and it is not recommended for patients at low risk (<10%) of neutropenic fever.[48]

The NCCN guidelines state that there is less evidence for therapeutic use than for prophylactic use. If patients with acute neutropenic fever are receiving prophylactic filgrastim or sargramostim, the CSF treatment should be continued. Pegfilgrastim should be discontinued, as it is long-acting and evidence for its therapeutic benefits is lacking. If the patient is not receiving prophylactic CSF, their risk of infection complications or poor outcome should be assessed. CSF should be considered for patients at high risk.[48]

The NCCN guidelines affirm the effectiveness of G-CSF therapy for SCN, CN, and congenital neutropenia. Patients with cyclic or idiopathic neutropenia appear to benefit at lower doses of G-CSF than those with congenital neutropenia. Patients with severe congenital neutropenia, requiring high doses of G-CSF, seem to be at greater risk of AML and MDS.[48]

European guidelines also recommend prophylactic treatment with G-CSFs in patients receiving chemotherapy regimens that pose a high risk of febrile neutropenia.With chemotherapy regimens associated with moderate risk, primary prophylaxis may also be advisable for cases in which patient-related factors increase the overall risk, or to maintain chemotherapy in cases where dose-dense or dose-intense chemotherapy strategies are used because of survival benefits, or reductions in chemotherapy dose intensity or density are known to be associated with a poor prognosis.[49]

Primary prophylaxis with biosimilar filgrastim has been shown to be cost-effective.[50] Biosimilar filgrastim has also been recommended for approval in the United States.ref53}


Granulocyte Transfusion

Neutrophil (granulocyte) transfusions have undergone a cycle of popularity followed by disfavor. These transfusions are accompanied by many complications, including severe febrile reactions. Their use is controversial.

Although disappearing from clinical practice, granulocyte transfusions have some clinical usefulness in treating neonatal sepsis. Their usefulness in adults with neutropenia, in whom adequate increments of WBC counts are difficult to achieve, has not been demonstrated in randomized clinical trials.[51] Granulocyte transfusion could be considered in cases of gram-negative sepsis with no improvement in 24-48 hours.


Other Medical Measures

Other measures that may be taken in the care of the patient with neutropenia include the following:

  • Corticosteroid therapy (potentially effective in immune-mediated neutropenia)
  • Correction of nutritional (eg, cobalamin or folic acid) deficiency if detected
  • In cases caused by heavy metals such as gold, chelation with British anti-Lewisite (dimercaprol)
  • Careful handwashing before and after direct contact with patients with neutropenia
  • Meticulous care of indwelling venous catheters and avoidance of urinary catheters and other invasive maneuvers that violate natural infection barriers

Splenectomy and Other Surgical Procedures

In individuals with neutropenia and Felty syndrome who have recurrent life-threatening bacterial infections, splenectomy is the treatment of choice, though the response is often short lived. Systemic lupus associated with autoimmune agranulocytosis may also respond to splenectomy or to immunosuppressive therapy. Idiopathic autoimmune neutropenia may also respond to immune therapy.[14]

Indwelling central venous catheters should be removed in febrile neutropenic patients if septic thromboembolism is suspected. Other indications for catheter removal include the following:

  • Corynebacterium jeikeium infection
  • Infection with Candida species
  • Polymicrobial infection
  • Persistent fevers
  • Pocket-space abscess
  • Tunnel infections

In general, surgery should be avoided in a patient with neutropenia; however, surgical drainage of abscesses that have pus or watery exudate under pressure may occasionally be lifesaving. Perirectal abscesses and cholecystitis with cholangitis are examples of infections that, if left undrained, lead to polymicrobial sepsis, despite antibiotic therapy.


Dietary Measures

Neutropenic patients should follow the following dietary restrictions:

  • Avoid raw and undercooked meat or well water
  • Commercial fruit juices, beer, milk, and milk products should be pasteurized
  • Aged cheese and cheese-based dressings should not be used
  • Avoid unwashed raw fruits and vegetables; these may contain large numbers of bacteria. All food should be cooked. Fresh flowers should be avoided as well
  • Outdated products and all moldy products should not be consumed

In patients with periodontitis and stomatitis, a soft or full liquid diet is indicated. Spicy and acidic foods should be avoided until recovery is complete.



Request a hematology consultation for review of the bone-marrow slides and peripheral blood smears to confirm the diagnosis and to assist in G-CSF dosing and evaluation.

Request an infectious disease consultation for advice and assistance in the selection of appropriate antibiotics, especially in patients with complicated infections or prolonged neutropenic fever that is not responding to standard therapy.


Long-Term Monitoring

Obtain daily CBC counts with manual differential to monitor the neutropenic patient’s recovery from an etiologic agent or to monitor the neutropenia’s response to G-CSF or GM-CSF.

If septic shock occurs, the patient should be transferred to the ICU. Intubation may be required.

Contributor Information and Disclosures

Christopher D Braden, DO Hematologist/Oncologist, Chancellor Center for Oncology at Deaconess Hospital

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Emmanuel C Besa, MD Professor Emeritus, Department of Medicine, Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Kimmel Cancer Center, Jefferson Medical College of Thomas Jefferson University

Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American Society of Clinical Oncology, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Karen Seiter, MD Professor, Department of Internal Medicine, Division of Oncology/Hematology, New York Medical College

Karen Seiter, MD is a member of the following medical societies: American Association for Cancer Research, American College of Physicians, American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching; Received consulting fee from Novartis for speaking and teaching; Received honoraria from Celgene for speaking and teaching.


Ariel Distenfeld, MD Clinical Professor, Department of Medicine, New York University School of Medicine

Disclosure: Nothing to disclose.

John E Godwin, MD, MS Professor of Medicine, Chief Division of Hematology/Oncology, Associate Director, Simmons Cooper Cancer Institute, Southern Illinois University School of Medicine

John E Godwin, MD, MS is a member of the following medical societies: American Association for the Advancement of Science, American Heart Association, and American Society of Hematology

Disclosure: Nothing to disclose.

Kush Sachdeva, MD Southern Oncology and Hematology Associates, South Jersey Healthcare, Fox Chase Cancer Center Partner

Disclosure: Nothing to disclose.

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Bilateral interstitial infiltrates in a 31-year-old patient with influenza pneumonia.
Anteroposterior chest radiograph in a young ED patient presenting with cough and malaise. The radiograph shows a classic posterior segment right upper lobe density consistent with active tuberculosis. This woman was admitted to isolation and started empirically on a 4-drug regimen in the ED. Tuberculosis was confirmed on sputum testing. Image courtesy of Remote Medicine,
Lateral chest radiograph in a 31-year-old patient with influenza pneumonia. Image courtesy of Remote Medicine,
The margins of this massive spleen were palpated easily preoperatively. Medially, the 3.18-kg (7-lb) spleen crosses the midline. Inferiorly, it extends into the pelvis.
Doppler sonogram at the splenic hilum reveals hepatofugal venous flow in a patient with portal hypertension.
Table 1. Genetic (Hereditary) Conditions in Agranulocytosis [24]
Syndrome Inheritance Gene Clinical Features
Cyclic neutropenia Autosomal dominant ELA2 Alternate 21-day cycling of neutrophils and monocytes
Kostmann syndrome Autosomal recessive Unknown Stable neutropenia, no MDS or AML
Severe congenital neutropenia Autosomal dominant ELA2 (35-84%) Stable neutropenia, MDS or AML
Autosomal dominant GFI1 Stable neutropenia, circulating myeloid progenitors, lymphopenia
Sex linked Wasp Neutropenic variant of Wiskott-Aldrich syndrome
Autosomal dominant G-CSFR G-CSF–refractory neutropenia, no AML or MDS
Hermansky-Pudlak syndrome type 2 Autosomal recessive AP3B1 Severe congenital neutropenia, platelet dense-body defect, oculocutaneous albinism
Chediak-Higashi syndrome Autosomal recessive LYST Neutropenia, oculocutaneous albinism, giant lysosomes, impaired platelet function
Barth syndrome Sex linked TAZ Neutropenia, often cyclic; cardiomyopathy, methylglutaconic aciduria
Cohen syndrome Autosomal recessive COH1 Neutropenia, mental retardation, dysmorphism
Source: Modified from Berliner et al, 2004.[24]

AML = acute myeloid leukemia; G-CSF = granulocyte colony-stimulating factor; MDS = myelodysplastic syndrome.

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